SUMMARY We are requesting funds to acquire a high-sensitivity mass spectrometer Qtrap 6500+ from SCIEX. The instrument will support users involved in anti-infective research, with a focus on the quantitation and spatial distribution of antibiotics as well as investigational new drugs. The instrument will be located in the Analytical and Imaging Facility of the Public Health Research Institute at the New Jersey Medical School of Rutgers University. A team of qualified personnel is available on-site to manage and operate the instrument as part of a well-established analytical platform supported by the NJMS and PHRI. The research projects include the quantitation of drugs active against HIV, tuberculosis and fungal pathogens in plasma and at the sites of infection, in both clinical samples and animal models. The highly sensitive instrument will overcome many of the current limitations we experience due to either small sample volumes or low drug levels. Working with small sample volumes increases throughput, reduces the number of animals required in pharmacokinetic and pharmacodynamic studies, and enables drug quantitation in challenging but important matrices such as vaginal swabs and dried blood spots. We have recently developed a novel method to achieve spatial quantitation of drugs and lipids using laser-capture microdissection combined with high- pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The Qtrap 6500+ will leverage the capabilities of this pioneering method since it will allow for reducing the amount of micro-dissected material required to achieve accurate quantitation, thus improving spatial resolution. Another set of projects focus on the detection and quantitation of biomarkers of pathology, disease progression and drug response in plasma, urine and tissues. Again, the high sensitivity of the proposed instrument will be key to the success of these projects due to the low abundance of some of these biomarkers, and the small volumes of samples collected by laser-capture microdissection. A high accuracy mass spectrometer in our well-supported facility will expand and promote research opportunities for both neglected and less neglected infectious diseases. With the new Sciex 6500, our analytic capabilities will reach the next level of sensitivity and spatial quantitation and place PHRI on the global map of anti-infective research.